Impaired arm function is a major cause of chronic disability among stroke survivors. A number of treatment approaches have been developed to facilitate the recovery of arm function, targeting stroke induced motor impairments such as paresis, spasticity and losses of independent joint control that result in involuntary elbow, wrist and finger flexion while lifting the arm (i.e., the flexion synergy). However, our understanding of how muscle adapts to these impairments over time is not clear at this juncture nor how changes in muscle properties impact the functional use of the paretic arm. Therefore, we propose to determine the extent of structural changes in the skeletal muscles of the paretic arm due to the persistence of a prominent flexion synergy, paresis, and the associated disuse of the paretic upper limb. Subsequently, we propose to demonstrate the effects of these secondary musculoskeletal changes on the ability to generate functional arm movements by using novel simulations of combined arm and hand motion. We postulate that the flexion synergy, paresis, and the chronic disuse of the paretic upper limb that results from the stroke, induce substantial changes in both passive and active muscle properties, thus limiting the ability to generate functional arm movements, even if normal neural drive from the brain would be restored. In Aim 1, we propose to investigate the relationship between the abnormal flexion synergy and increases in passive stiffness that result in more flexed arm postures in individuals with stroke. In Aim 2 we propose to characterize changes in muscle architectural parameters (i.e., fascicle and sarcomere length, and muscle volume) following stroke and determine the effect of any structural deviations from age-matched able-bodied individuals on maximum isometric force generation ability, as indicated by calculating muscle physiological cross-sectional area, a standard anatomical measure of an individual muscle's ability to generate force. Finally, as part of Aim 3 we propose to employ state-of-the-art forward dynamics simulation techniques using an upper limb model that integrates the arm and hand to determine the extent to which altered muscle properties (Aims 1 & 2) and abnormal muscle co-activation patterns (Aim 1) account for the severe limitations in functional use of the upper limb experienced by individuals with chronic hemiparetic stroke. The rationale that underlies the proposed research is that determining the exact role of altered muscle properties on functional use of the paretic upper limb following chronic hemiparetic stroke will allow for the design of more effective rehabilitation interventions This will change the way clinicians approach the rehabilitation of the paretic upper limb by highlighting the relative importance of the various musculoskeletal changes which combined with the proposed measurement tools provide the means to design and test therapies to reduce or prevent detrimental changes in muscle following stroke.